A new dual laser system utilizing fluorescence spectroscopy as a guidance modality for pulsed dye laser tissue ablation has been studied in 70 patients with femoropopliteal occlusions as part of a cooperative multi-center evaluation. This device, originally conceived and developed as a product of joint NIH-industry research is now being used in 10 centers in the United States and France. The system is unique among laser angioplasty devices in that real-time guidance of the treatment laser is provided utilizing florescence spectroscopic identification of proposed target sites which should greatly improve recanalization efficacy and reduce the frequency of transmural perforations. The patients treated in this study had femoropopliteal occlusions of varying lengths which could not be treated successfully using standard balloon angioplasty techniques. In this patient cohort, primary recanalization using the single fiber laser device was successful in 81% of patients followed by successful balloon angioplasty in 74% of patients. Their were no major complications and florescence spectroscopy was helpful in identifying thrombus, in situations of flush main channel occlusions terminating in a large branch collateral vessel, and under circumstances when eccentric fiber position approached underlying media threatening vessel wall perforation. We believe that this advanced laser angioplasty system with real-time guidance capabilities will be an important tool in the treatment of coronary and peripheral vascular disease.